CHICAGO--(BUSINESS WIRE)--Celgene Corporation (NASDAQ:CELG) and Agios Pharmaceuticals, Inc.
(NASDAQ:AGIO) today announced new efficacy and safety data from the
ongoing Phase 1 dose-escalation and expansion study evaluating
investigational oral IDHIFA® (enasidenib) in patients with
relapsed or refractory acute myeloid leukemia (R/R AML) and an
isocitrate dehydrogenase-2 (IDH2) mutation. IDHIFA is an investigational
first-in-class, oral, targeted inhibitor of the mutant IDH2 enzyme,
which demonstrated an overall response rate of 40.3 percent, including a
complete response rate of 19.3 percent in the study. The data were
presented in an oral session at the American Society of Clinical
Oncology (ASCO) Annual Meeting and simultaneously published online in
the journal Blood.*

“The updated results, including duration of response, from the Phase 1
study reinforce the potential for enasidenib as a first-in-class therapy
for patients with relapsed or refractory AML and an IDH2 mutation,” said
Michael Pehl, President, Hematology/Oncology at Celgene. “Patients have
very few treatment options for relapsed or refractory AML, so we are
eager to advance this potential targeted therapy as quickly as possible.”

As of April 15, 2016, a total of 239 patients with advanced hematologic
malignances and an IDH2 mutation were enrolled into the Phase 1 study,
of which 176 patients had R/R AML. Data reported include patients
receiving enasidenib at total daily doses ranging from 50 mg to 650 mg
in the dose-escalation arm and 100 mg once daily in the Phase 1
expansion arms. A maximum tolerated dose was not reached. The median age
of the patients enrolled in the study is 70 (ranging from 19-100).
Patients with R/R AML received a median of two prior lines of therapy
(ranging from one to 14).

Data from 176 R/R AML patients with an IDH2 mutation demonstrated a 40.3
percent (71 of 176 patients) overall response rate, which was the
primary endpoint of the study. Further, the complete response rate was
19.3 percent (34 of 176 patients). Median duration of response was 5.8
months [95% CI 3.9, 7.4] for all patients who responded and 8.8 months
[95% CI 6.4, NR] for patients who achieved a CR. Median time to first
response was 1.9 months (0.5-9.4) and median time to CR was 3.8 months
(0.5-11.2). Median overall survival (OS) for R/R AML patients as
observed in the study was 9.3 months [95% CI 8.2, 10.9]. Additional
results including qualitative improvement in response over time,
improvement in hematological parameters over time, OS for patients
achieving a CR and transfusion independence were also reported.

“In addition to the complete response in this study, we also observed
changes in responses and hematologic parameters over time,” said Eytan
Stein, M.D., lead investigator and attending physician in the leukemia
service at Memorial Sloan Kettering Cancer Center. “This suggests that
differentiation of myeloblasts – made possible by inhibition of mutated
IDH2 – may drive the clinical efficacy of enasidenib.”

“Targeting IDH mutations is thought to allow for the differentiation of
malignant cells and introduces a new paradigm in the treatment of AML,”
said Chris Bowden, M.D., chief medical officer of Agios. “These data
show that IDH inhibition plays an important role in segments of AML and
will continue to inform our research into this novel class of potential
therapies.”

A separate analysis of IDH-inhibitor-associated differentiation syndrome
(IDH-DS) associated with enasidenib was also presented as a poster
discussion during the ASCO meeting and detailed the findings of an
independent Differentiation Syndrome Review Committee (DSRC). The
committee reviewed investigator reported IDH-DS cases and determined
that 13 of the 27 potential cases were consistent with IDH-DS (11.9% of
109 patients). These data demonstrate that the signs and symptoms of
IDH-DS are recognizable. IDH-DS represents a novel clinical finding in
patients with mutated IDH2 AML treated with enasidenib, and is likely
due to its purported mechanism of action, differentiation of leukemic
cells.

In addition to the clinical data publication, additional analyses
describing the mechanism of action of enasidenib were also published
online in Blood. An analysis of patient samples confirmed that
the preclinical efficacy and mechanism of action of mutated IDH2
inhibition by enasidenib is through differentiation of AML cells. The
authors conclude that the data provide insights into enasidenib
resistance to inform future mechanism-based combination treatment
studies.

Clinical Development

Enasidenib continues to be studied in the following ongoing clinical
trials:

Phase 1b study of either enasidenib or ivosidenib in combination with
standard induction and consolidation chemotherapy in newly diagnosed
AML (NCT02632708)

Phase 1/2 study of either enasidenib or ivosidenib in combination with
azacitidine in newly diagnosed AML (NCT02677922)

The New Drug Application (NDA) for IDHIFA is currently under Priority
Review with the U.S. Food and Drug Administration for the treatment of
patients with relapsed or refractory AML with an IDH2 mutation. The NDA
has been given a Prescription Drug User Fee Act (PDUFA) action date of
Aug. 30, 2017.

Study AG221-C-001 includes three parts: a Phase 1 dose escalation, a
part 1 (Phase 1) expansion and a Phase 2 expansion.

The Phase 1 dose escalation study was designed to determine the maximum
tolerated dose and recommended Phase 2 dose, and to evaluate efficacy
and safety of enasidenib (AG-221/CC-90007) in subjects with advanced
hematologic malignancies with an IDH2 mutation. The Part 1 expansion
further evaluated the safety, tolerability, and efficacy of enasidenib
in subjects with R/R AML, untreated AML, myelodysplastic syndrome or
other advanced hematologic malignancies with an IDH2 mutation. Based on
the clinical activity observed in R/R AML subjects, the Phase 2
expansion was designed to assess efficacy of enasidenib at recommended
100 mg daily dose and to further evaluate safety in subjects with R/R
AML and with IDH2 mutation. The study was not designed or statistically
powered to reach a conclusion on OS. A phase 3 randomized controlled
trial with OS as a primary endpoint has been initiated.

About Acute Myelogenous Leukemia (AML)

AML, a cancer of blood and bone marrow characterized by rapid disease
progression, is the most common acute leukemia affecting adults.
Undifferentiated blast cells proliferate in the bone marrow rather than
mature into normal blood cells. AML incidence significantly increases
with age, and according to the American Cancer Society, the median age
of onset is 66. The vast majority of patients do not respond to
chemotherapy and progress to relapsed/refractory AML. The five-year
survival rate for AML is approximately 20 to 25 percent. IDH2 mutations
are present in about 8 to 19 percent of AML cases.

About Agios

Agios is focused on discovering and developing novel investigational
medicines to treat cancer and rare genetic diseases through scientific
leadership in the field of cellular metabolism. In addition to an active
research and discovery pipeline across both therapeutic areas, Agios has
multiple first-in-class investigational medicines in clinical and/or
preclinical development. All Agios programs focus on genetically
identified patient populations, leveraging our knowledge of metabolism,
biology and genomics. For more information, please visit the company's
website at www.agios.com.

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global biopharmaceutical company engaged primarily in the
discovery, development and commercialization of innovative therapies for
the treatment of cancer and inflammatory diseases through
next-generation solutions in protein homeostasis, immuno-oncology,
epigenetics, immunology and neuro-inflammation. For more information,
please visit www.celgene.com.
Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.

About Agios/Celgene Collaboration

IDHIFA® (enasidenib) and AG-881 are part of Agios' global
strategic collaboration with Celgene Corporation focused on cancer
metabolism. Under the terms of the 2010 collaboration agreement, Celgene
has worldwide development and commercialization rights for IDHIFA. Agios
continues to conduct clinical development activities within the IDHIFA
development program and is eligible to receive reimbursement for those
development activities and up to $95 million in remaining payments
assuming achievement of certain milestones and royalties on net sales.
Celgene and Agios intend to co-commercialize IDHIFA in the U.S. Celgene
will reimburse Agios for costs incurred for its co-commercialization
efforts.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements, which are
generally statements that are not historical facts. Forward-looking
statements can be identified by the words "expects," "anticipates,"
"believes," "intends," "estimates," "plans," "will," “outlook” and
similar expressions. Forward-looking statements are based on
management’s current plans, estimates, assumptions and projections, and
speak only as of the date they are made. Neither Celgene nor Agios
undertake any obligation to update any forward-looking statement in
light of new information or future events, except as otherwise required
by law. Forward-looking statements involve inherent risks and
uncertainties, most of which are difficult to predict and are generally
beyond each company’s control. Actual results or outcomes may differ
materially from those implied by the forward-looking statements as a
result of the impact of a number of factors, many of which are discussed
in more detail in the Annual Report on Form 10-K and other reports of
each company filed with the Securities and Exchange Commission.

Hyperlinks are provided as a convenience and for informational
purposes only. Neither Celgene nor Agios bears any responsibility for
the security or content of external websites.